The overall goal of this research is to investigate synaptic mechanisms subserving cardiovascular reflex integration at central nervous system level using neurophysiological and neuropharmacological techniques. This proposal focuses on synaptic events occurring at the first stage of the central cardiovascular reflex pathway in nucleus tractus solitarius (NTS). Bilateral electrical stimulation of the carotid sinus nerves (CSNs) and selective stimulation of chemoreceptors and baroreceptors traveling in CSNs will be combined with extracellular and intracellular single unit recordings in NTS to determine the manner in which NTS neurons process convergent afferent input from cardiovascular sensory receptors. The influence of one higher cardiovascular-related brain stem center, the parabrachial nucleus (PBN), in modulating CSN inputs to NTS will be studied and the possibility that there may be a direct feedback mechanism whereby PBN inhibits cardiovascular afferent input to NTS will be addressed. An assessment will be made of the integrated output signal transmitted from NTS to PBN, and the responses of PBN neurons to selective stimulation of baroreceptor and chemoreceptor inputs will be assessed to determine the extent of afferent intergration which has occurred at the level of a secondary projection nucleus. Finally, we will pursue the cardiovascular-related role of PBN using microinjection techniques to map the sites within this nucleus from which neuronally mediated pressor responses can be obtained, to evaluate the relationship of this pressor response to the baroreceptor modulated depressor response mediated through NTS, and to determine whether neurotransmitter substances identified in neurons projecting from NTS to PBN evoke similar processor responses. Although the present studies focus specifically on baroreceptor and chemoreceptor inputs from one representative pair of cardiovascular afferent nerves, it is anticipated that the study of interactions of two receptor types in NTS, the site of primary afferent termination in the brain stem, and PBN, its major secondary projection nucleus, will yeild new information regarding the neuronal mechanisms involved in reflex regulation of arterial pressure and heart rate. In the long term, investigations of these mechanisms may be of value in understanding the role of the central nervous system in derangements of circulatory control in pathological conditions such as hypertension and heart failure.